Infants born to obese and overweight mothers have increased adiposity and the biological mechanisms underlying this relationship remain elusive. Animal models suggest the gut microbiome may be an important factor mediating the transfer of obesity risk from mother to infant during pregnancy, yet information defining how maternal features such as obesity impacts microbial colonization and infant adiposity remains unclear. This proposal is devoted to understanding the how maternal obesity acts to reprogram the microbiome of the mother-infant pairs during the first 4 months of life and establish how this critical window of development impacts maternal characteristics, the infant microbiome, and infant adiposity. The overarching hypothesis of this proposal is that the maternal microbiome in mothers with distinct phenotypes (from normal weight to obese) will directly affect the development of the infant's microbiome and adiposity during the first 4 months of life. Under this award, we will analyze a subset of data from an ongoing longitudinal cohort study that has comprehensively characterized 40 mother-infant pairs over the first 4-months of life. The maternal phenotypes in this study are selected according to mother-infant pairs (n=20) in each of the following study groups: normal weight (NW) and obese (Ob). Maternal stool and human milk samples will be used to characterize maternal microbial exposure and infant stool samples will be used to characterize the infant microbiome. The specific questions addressed in this proposal are three-fold: 1) determine how obesity impacts the maternal microbiome during late pregnancy and through the first 4 months postpartum; 2) determine how infant exposure to the maternal microbiome among women with obesity affects the infant microbiome during the first 4 months of life; and finally 3) determine whether the maternal-infant microbiome is a major determinants of infant adiposity through the first 4 months of life. The results of this project wil provide a deep understanding of how maternal obesity acts to reprogram the microbiome in mother-infant pairs and help to dissect the mechanisms linking maternal characteristics to infant adiposity through changes to the human microbiome.